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The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K–PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds. 相似文献
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The Editor-in-Chief has retracted the published paper "ProtectiveEffects of 相似文献
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Employing the arts for knowledge production and translation: Visualizing new possibilities for women speaking up about safety concerns in maternity
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de Koning JP; Dong F; Smith L; Schelen AM; Barge RM; van der Plas DC; Hoefsloot LH; Lowenberg B; Touw IP 《Blood》1996,87(4):1335-1342
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Using flow cytometry and osmotic lysis measurements, we document here the means and coefficients of variation of the following red cell (RBC) properties: hemoglobin (Hb) content, volume, Hb concentration, and relative lytic tonicity distributions in populations of normal human RBCs, before and after density fractionation. The distributions showed a pattern characterized by much larger coefficients of variation of the Hb content and volume distributions than of the Hb concentration and relative lytic tonicity distributions. From analysis of the factors that determine those RBC properties, the patterns were interpreted as reflecting previously unrecognized statistical proportionalities between cell osmolyte content, Hb content, and membrane area. The possible origin of these statistical links was analyzed by considering alternative models with and without the participation of regulatory processes during cell maturation. A model was shown to be feasible in which mature RBC variability with proportional volume, area, and Hb content arises solely from cell size variability at the last erythroid cell division. 相似文献
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O'Malley CJ; Rasko JE; Basser RL; McGrath KM; Cebon J; Grigg AP; Hopkins W; Cohen B; O'Byrne J; Green MD; Fox RM; Berndt MC; Begley CG 《Blood》1996,88(9):3288-3298
This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status. 相似文献
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Kath Padgett BSc MA PGDip Cert Ed RMN Christine Rhodes BSc MSc RGN RM RN Child RHV Maureen Lumb Penny Morris BA Sue Sherwin BA MA PGCHE RMN Jools Symons BA MA Joannie Tate Ken Townend 《Health expectations》2014,17(3):418-428
Background Involving service users and carers in decisions about their health care is a key feature of health‐care practice. Professional health and social care students need to develop skills and attributes to best enable this to happen. Aims The aims were to explore service user and carer perceptions of behaviours, attributes and context required to enable shared decision making; to compare these perceptions to those of students and academic staff with a view to utilizing the findings to inform the development of student assessment tools. Methods A mixed methods approach was used including action learning groups (ALG) and an iterative process alongside a modified Delphi survey. Participants The ALGs were from an existing service user and carer network. The survey was sent to sixty students, sixty academics and 30 service users from 16 different professional disciplines, spanning four Universities in England. Results The collaborative enquiry process and survey identified general agreement that being open and honest, listening, showing respect, giving time and being up to date were important. The qualitative findings identified that individual interpretation was a key factor. An unexpected result was an insight into possible insecurities of students. Conclusions The findings indicate that distilling rich qualitative information into a format for student assessment tools could be problematic as the individual context could be lost, it is therefore proposed that the information could be better used as a learning rather than assessment tool. Several of those involved identified how they valued the process and found it beneficial. 相似文献